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A study for the induction of transplantation tolerance using adenovirus expressing PD-1 ligands and application to myoblast transplantation into infarcted hearts.

Research Project

Project/Area Number 15390415
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

SAKAKIDA Satoru  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90311753)

Co-Investigator(Kenkyū-buntansha) SHIRAKURA Ryota  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
SAWA Yoshiki  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00243220)
FUKUSHIMA Norihide  Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (30263247)
MATSUMIYA Goro  Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (20314312)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordsimmunological tolerance / transplantation / co-stimulatory molecules / 組み替えアデノウイルス / 筋芽細胞 / PD-1リガンド / PD1 / T細胞
Research Abstract

We have generated five new recombinant adenovirus that express mouse B7.1, B7.2, PDL-1, PDL-2, or ICOS ligand and used them to study immunoregulatory functions of the proteins on alloimmune responses. The results are summarized as below.
1. Introductions of cDNA for all the molecules were successful. The generated E1/E3 defective non-reproductive recombinant adenovirus woll become new research resources uniquely generated by this project.
2. The generated adenovirus could be easily infected to adherent mammalian cells including cultured skeletal myoblasts and HeLa cells and effectively induced surface expression of the introduced molecules. However, it was difficult to infect and induce the expression on non-adherent cells such as those of lymphoid origin, even if the cells from the Coxsackie-Adenovirus receptor transgenic animals were used.
3. Threfore, it was impossible to test the possibility if the generated virus could improve the efficacy of the ability to induce allogeneic tolerance by the intravenous presensitization of hosts with allogeneic lymphoid cells. Alternatively, we have tested the immunomodulatory functions of the molecules in vivo by measuring anti-adenovirus antibodies by hosts which had been infected with the generated recombinant virus. As a results, PDL-1 but not PDL-2 was suggested to have immunosuppressive effects on anti-virus immune reaction. The effect, however, was weaker if it was compared to that observed by the injection of adenovirus expressing CTLA4-Ig, a well-known immunosuppressant and a blocker of CD28-B7 interactions.
4. Autologous skeletal myoblasts implantation was established as a possible therapeutic method to improve failed cardiac functions of infarcted rat hearts. It would be a strategy to treat myocardial infarction in future that allogeneic skeletal myoblasts will be modified to express PDL-1 on their surface and transplanted on the impaired hearts as the sheet to restore the cardiac functions.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (19 results)

All 2005 2004 2003 Other

All Journal Article (17 results) Publications (2 results)

  • [Journal Article] Mocroarray-based gene expression profiling of retransplanted rat cardiac allografts that develop cardiac allograft vasculopathy.2005

    • Author(s)
      S.Kitagawa-Sakakida et al.
    • Journal Title

      The Journal of Heart and Lung Transplantation 24(12)

      Pages: 2068-2074

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion injury in rat heart.2005

    • Author(s)
      AN.Aleshin, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology 38(3)

      Pages: 517-525

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repair of impaired myocardium by implantation of Engineered Autologous Myoblast sheets.2005

    • Author(s)
      IA Memmon, et al.
    • Journal Title

      Journal of Thoracic and cardiovascular Surgery 130(3)

      Pages: 1333-1341

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene transfection of hepatocyte growth factor attenuates the progression of cardiac remodeling in the hypertrophied heart.2005

    • Author(s)
      K.Iwata, et al.
    • Journal Title

      Journal of Thoracic and cardiovascular Surgery 130(3)

      Pages: 719-725

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microarray-based gene expression profiling of retransplanted rat cardiac allografts that develop cardiac allograft vasculopathy.2005

    • Author(s)
      S.Kitagawa-Sakakida, et al.
    • Journal Title

      J Heart Lung Transplant 24

      Pages: 2068-2074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion injury in rat heart2005

    • Author(s)
      AN Aleshin, et al.
    • Journal Title

      J Mol Cell Cardiol 38

      Pages: 517-525

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene transfection of hepatocyte growth factor attenuates the progression of cardiac remodeling in the hypertrophied heart.2005

    • Author(s)
      K.Iwata, et al.
    • Journal Title

      J Thorac Cardiovasc Surg 130

      Pages: 719-725

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repair of impaired myocardium by implantation of Engineered Autologous Myoblast sheets.2005

    • Author(s)
      IA Memmon, et al.
    • Journal Title

      J Thorac Cardiovasc Surg 130

      Pages: 1333-1341

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mocroarray-based gene expression profiling of retrasplanted rat cardiac allografts that develop cardiac allograft vasculopathy.2005

    • Author(s)
      S.Kitagawa-Sakakida et al.
    • Journal Title

      The Journal of Heart and Lung Transplantation 24(12)

      Pages: 2068-2074

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 150-kDa oxygen-regulated protein attenuates mycardial ischemia-reperfusion injury in rat heart.2005

    • Author(s)
      AN.Aleshin, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology 38(3)

      Pages: 517-525

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Repair of impaired myocardium by implantation on Engineered Autologous Myoblast sheets.2005

    • Author(s)
      IA Memmon, et al.
    • Journal Title

      Journal of Thoracic and cardiovascular Surgery 130(3)

      Pages: 1333-1341

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gene transfection of hepatocyte growth factor attenuates the progression ofcardiac remodeling in the hypertrophied heart.2005

    • Author(s)
      K.Iwata, et al.
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery 130(3)

      Pages: 719-725

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion injury in rat heart.2005

    • Author(s)
      Aleshin AN, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 重症虚血性心疾患に対するHGF遺伝子や細胞移植による血管新生治療法2004

    • Author(s)
      宮川繁, 他
    • Journal Title

      医工学治療 16(2)

      Pages: 103-107

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antibody deposition in rat hearts which develops transplant vasculopathy in (donor x recipient) F1 environment.2003

    • Author(s)
      Z.Li, et al.
    • Journal Title

      Surgery Today 33

      Pages: 509-517

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antibody deposition in rat hearts which develops transplant vasculopathy in (donor x recipient)F1 environment.2003

    • Author(s)
      Z.Li, et al.
    • Journal Title

      Surgery Today 33

      Pages: 509-517

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Re-organization of cytoskeletal proteins and prolonged life expectancy caused by hepatocyte growth factor in a hamster model of late-phase dilated cardiomyopathy.

    • Author(s)
      Kondoh K, et al.
    • Journal Title

      Journal of Thoracic and Cardiovascular Surgery (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Publications] Z.Li, S.Kitagawa-Sakakida, K.Horiguchi et al.: "Antibody deposition in rat heart which develops transplant vasculonathy in (Donor x Recipient) E1 environment"Surgery Today. 33. 509-517 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 榊田悟ほか共著者51名: "免疫・アレルギー疾患用語解説集"エクセル企画出版. 347 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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